PATHOPHYSIOLOGY AND TREATMENT OF CLINICALLY RESISTANT CYTOMEGALOVIRUSRETINITIS

Purpose: To determine the incidence, pathophysiology, clinical outcome , and survival in patients with clinically resistant retinitis. Method s: Cytomegalovirus (CMV) retinitis was prospectively studied in 100 pa tients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new ac tivity or progression, despite at least 8 consecutive weeks of inducti on doses of either foscarnet or ganciclovir. Fundus photography, pharm acokinetics, CMV cultures and sensitivities, and survival analyses wer e studied. The therapeutic interventions attempted after clinically re sistant retinitis was identified included continuing a high dose (indu ction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir. Result s: Clinically resistant retinitis occurred in 11 (11%) of 1 00 patient s with CMV retinitis and appeared to be a manifestation of acquired CM V antiviral drug resistance. Drug metabolism and pharmacokinetics in t hese patients were normal. The use of combination therapy with foscarn et and ganciclovir was effective in halting the progression of retinit is in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy. Conclusion: Clinically resistant retini tis is a manifestation of infection by CMV that has acquired drug resi stance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive l onger.